Azacytidine and Lymphocytes in Relapse of AML or MDS After Allogeneic Stem Cell Transplantation.

• Status: Completed
• Trial end date: 2019-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The present project is a multicenter, phase II trial which aims at evaluating if the administration of azacytidine (Vidaza®) combined to donor lymphocyte infusion (DLI) could improve the response rate to DLI in the population of patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Carlos Graux, MD, PhD
• Collaborators: Belgian Hematological Society; Celgene Corporation
• Treatments: Azacitidine

Criteria

Inclusion Criteria:

1. Patients:

• Age ≥ 18 years

• Be able to understand and sign informed consent

• Fertile patients must use a reliable contraception method

2. Disease status at transplantation:

• AML in first or subsequent complete remission (< 5% marrow blasts)

• MDS with less than 10% marrow blasts at the time of transplantation

3. Transplantation:

• Allogeneic transplantation using a sibling or unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of one allele or one antigen or 1 antigen + 1 allele or 1 antigen + 1 DQB1 antigen or 2 alleles mismatches.

• Myeloablative or reduced-intensity conditioning

• Second transplantation is allowed

• Donor is willing to donate lymphocytes

4. Clinical situation:

• Cytological relapse after allo-SCT defined as the recurrence of more than 5% blasts on bone marrow aspiration (AML) or evidence of MDS

• Immunophenotypic relapse defined as the recurrence of an abnormal phenotype on flow cytometry in bone marrow aspirate (only in case of a specific phenotype).

• Cytogenetic or molecular relapse defined as the persistence or recurrence of a cytogenetic abnormality or molecular marker in bone marrow aspiration or peripheral blood. WT1 expression is not considered as reliable marker for relapse in this protocol but FLT3-ITD, NPM1, CEBPA, or translocation-specific markers (such as MLL-PTD, AML-ETO, CBFB-MYH11) are.

5. Immunosuppressive therapy should have been stopped before inclusion.

Exclusion Criteria:

• More than 30% marrow blasts at the time of inclusion

• Extramedullary relapse including CNS involvement

• ECOG Performance status > 2

• Active acute grade II-IV GvHD at the time of inclusion

• Active chronic GvHD requiring systemic therapy at the time of inclusion

• Uncontrolled infection

• HIV positive

• Acute or chronic heart failure (NYHA class III or IV) or symptomatic ischemic heart disease or ejection fraction < 35% or uncontrolled arrhythmia

• Severe liver failure (total bilirubin > 3 mg/dL, SGPT > 4 X upper normal limit)

• Severe pulmonary failure (corrected DLCo < 35%)

• Terminal renal failure requiring dialysis

• Severe neurological or psychiatric disorders

• Concurrent investigational drug.

• Other treatment for relapse, except for hydroxyurea but it should be stopped before inclusion in the study.

• Female who is pregnant or breastfeeding